High-quality nanocrystals formed in organic solvents can be completely solubilized in water using amphiphilic copolymers containing poly(ethylene glycol) or PEG. These copolymers are generated using a maleic anhydride coupling scheme that permits the coupling of a wide variety of PEG polymers, both unfunctionalized and functionalized, to hydrophobic tails. Thermogravimetric analysis, size exclusion chromatography, cryogenic transmission electron microscopy, and infrared spectroscopy all indicate that the copolymers effectively coat the nanocrystals surfaces. The composite nanocrystal-polymer assemblies can be targeted to recognize cancer cells with Her2 receptor and are biocompatible if their surface coatings contain PEG. In the particular case of semiconductor nanocrystals (e.g., quantum dots), the materials in water have the same optical spectra as well as quantum yield as those formed initially in organic solutions.
Nanoparticles, such as quantum dots (QDs), composed of biologically toxic materials degrade in highly oxidative environments. Varying the QD surface coating significantly affects the intracellular uptake of QDs. Although the addition of PEG does not alter the inherent QD cytotoxicity, we demonstrate that the improved biocompatibility due to PEG‐substitution arises from decreased intracellular uptake, which allows for biological applications of QDs with minimal toxicity. The image shows the live/dead reagent stain used to quantitate cytotoxicity. PEG: poly(ethylene glycol).
Advances in scattering-based optical imaging technologies offer a new approach to noninvasive point-of-care detection, diagnosis, and monitoring of cancer. Emerging photonics technologies provide a cost-effective means to image tissue in vivo with high resolution in real time. Advancing the clinical potential of these imaging strategies requires the development of optical contrast agents targeted to specific molecular signatures of disease. We describe the use of a novel class of contrast agents based on nanoshell bioconjugates for molecular imaging in living cells. Nanoshells offer significant advantages over conventional imaging probes including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. We show that nanoshell bioconjugates can be used to effectively target and image human epidermal growth factor receptor 2 (HER2), a clinically relevant biomarker, in live human breast carcinoma cells.
A facile method was developed for completely transferring high quality monodisperse iron
oxide nanocrystals from organic solvents to water. The as-prepared aqueous dispersions of
iron oxide nanocrystals were extremely stable and could be functionalized for
bioconjugation with biomolecules. These iron oxide nanocrystals showed negligible
cytotoxicity to human breast cancer cells (SK-BR-3) and human dermal fibroblast cells.
This method is general and versatile for many organic solvent-synthesized nanoparticles,
including fluorescent semiconductor nanocrystals.
Both photoswitchable fluorescent nanoparticles and photoactivatable fluorescent proteins have been used for super-resolution far-field imaging on the nanometer scale, but the photoactivating wavelength for such photochemical events generally falls in the near-UV (NUV) region (<420 nm), which is not preferred in cellular imaging. However, using two near-IR (NIR) photons that are lower in energy, we can circumvent such problems and replace NUV single-photon excitations (e.g., 390 nm) with NIR two-photon excitations (e.g., 780 nm). Thus, we have demonstrated that alternating 780 nm NIR two-photon and 488 nm single-photon excitations induces reversible on-off fluorescence switching of immunotargeted nanoparticles in the human breast cancer cell line SK-BR-3. Herein, two-photon absorption not only caused spiropyran-merocyanine photoisomerization within the particles but also imparted red fluorescence. In comparison with single-photon NUV excitations, two-photon NIR laser excitations can potentially reduce absorption-related photodamage to living systems because cellular systems absorb much more weakly in the NIR.
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